This is a revision of 1 R01 AA 015173-01. Recently (January 3, 2003), fluoxetine became the first SSRI antidepressant to be approved by the FDA for treatment of major depression (MDD) among adolescents and children. However, it is unclear whether this efficacy for fluoxetine extends to those with a comorbid alcohol use disorder (AUD), or whether it persists at long-term follow-up assessments. Many questions remain concerning the long-term course of this comorbid adolescent population, because no studies to date have addressed those crucial clinical questions. In the study being proposed, a first prospective long-term naturalistic follow-up study will be undertaken involving the comorbid DD/AUD) adolescents who are completing our ongoing double-blind placebocontrolled acute phase treatment study with fluoxetine (R01 AA13370). This proposed long-term naturalistic study will involve assessments at 2, 2.5, 3, 3.5, and 4 years following entry into our ongoing acute phase study. The time period involved in this proposed study covers the transition from late adolescence to early adulthood, which is a crucial developmental period that typically involves some adolescents decreasing or discontinuing alcohol use while others transition to lifelong dependence. The first goal of this proposed study is to evaluate the long-term efficacy of a previous 3-month acute phase course of fluoxetine versus placebo for the treatment of the pathological alcohol use and the depressive symptoms of comorbid (MDD/AUD) adolescents. We hypothesize that the therapeutic effects that fluoxetine demonstrated during the acute phase trial will persist at the follow-up assessments. The second goal of this proposed study is to characterize the long-term clinical course of treated MDD/AUD adolescents as they make the transition from late adolescence to early adulthood. We hypothesize that different outcome trajectories will be identifiable, and that at least one of those trajectories will be associated with the acute phase fluoxetine treatment. Other factors associated with those trajectories will include gender, age, persistent MDD at the completion of the acute phase study, a history of conduct disorder, and continuing vs. discontinuing psychotherapy.